1. Field of the Invention
The present invention relates generally to compositions and methods for formulating compositions for treatment of acne. More particularly, the present invention relates to compositions comprising benzoyl peroxide and clindamycin for treatment of acne by topical administration.
Acne is a common skin disorder characterized by blackheads, whiteheads, papules, pustules, cysts, and various sized nodules and scars which, in the inflammatory state of the disorder, are contaminated with bacteria such as Propionibacterium acnes. The disorder effects skin areas where the sebaceous glands are most active, and bacterial infection can occur in the sebaceous follicles.
A variety of acne treatment methods have been developed, D including both systemic and topical administration of antibiotics, topical administration of organic peroxides, particularly benzoyl peroxide, and the like. Of particular interest to the present invention is the topical administration of antibiotic compositions and other active ingredients, such as benzoyl peroxide.
A particularly effective topical composition for the treatment of acne is a combination of erythromycin, a topical antibiotic, and benzoyl peroxide, as described in U.S. Pat. No. 4,497,794. Compositions prepared generally as described in the '794 patent are sold under the tradename Benzamycin.RTM. by Dermik Laboratories, Inc., Collegeville, Pa. Benzamycin.RTM. is widely prescribed for the treatment of acne and is recognized in some cases to be more effective than treatment with either erythromycin or benzoyl peroxide alone.
The use of products which combine erythromycin and benzoyl peroxide, however, suffers from certain disadvantages. The combination of erythromycin and benzoyl peroxide is unstable and requires refrigeration for storage. The need to refrigerate the product is not only inconvenient for the patient (e.g., it is difficult to continuously refrigerate the product when travelling), the application of a cold medicine to the face is often unpleasant and reduces patient compliance. The need to store the product in a refrigerator can further reduce patient compliance since the product is "hidden away."
The Benzamycin.RTM. product suffers from particular formulation problems. In order to prepare the product, a pharmacist must dissolve erythromycin powder in alcohol from the pharmacy stock. Variations in particular alcohols which are available can lead to variability in the compounded product. Moreover, improper compounding by the pharmacist is possible because of the variable dissolution of erythromycin in alcohol resulting in partially dissolved or undissolved aggregates of the drug. As a result, the effective dosage of the compounded product can vary, and some patients have reported that the product sometimes feels "gritty" when applied to the skin.
For these reasons, it would be desirable to provide improved compositions and methods for formulating compositions for the treatment of acne. In particular, it would be desirable to provide products which combine the activity of an antibiotic compound with the activity of benzoyl peroxide, with none or fewer of the disadvantages described above for the combination of erythromycin and benzoyl peroxide. Such compositions should be effective in treating acne, preferably being at least as effective as the use of erythromycin/benzoyl peroxide compositions and more preferably being more effective than erythromycin/benzoyl peroxide compositions. The compositions should also overcome the formulation and stability problems which have been associated with the erythromycin/benzoyl peroxide compositions. That is, the improved compositions should be easy to formulate, should have a smooth consistency after formulation, should be adequately stable, and should have a sufficiently long storage life even without refrigeration.
2. Description of the Background Art
U.S. Pat. No. 4,497,794, discloses compositions combining erythromycin and benzoyl peroxide for the treatment of acne, as described above. Other patents disclosing the combination of erythromycin and benzoyl peroxide for acne treatment and other purposes include U.S. Pat. No. 4,411,893; U.S. Pat. No. 4,692,329; and British Patent No. 1,594,314. The combination of erythromycin with other organic peroxides for the treatment of acne is described in British Patent No. 2,088,717. Other formulations containing benzoyl peroxide for the treatment of acne are described in U.S. Pat. Nos. 3,535,422, 4,056,611; 4,318,907; 4,923,900; 4,387,107; and 4,228,163. Other peroxide formulations for treating acne are described in U.S. Pat. No. 4,607,101. The use of clindamycin and other lincomycin antibiotics for the treatment of acne is described in U.S. Pat. No. 3,969,516. Hirschmann (1988) Arch. Dermatol. 124:1691-1700 and Fulton, Jr., et al. (1974) Arch. Dermatol. 110:83-86 describe the topical use of antibiotics for the treatment of acne.